Modified t-PA with kringle-/replaced by another kringle

Details Modified t-PA with kringle-/replaced by another kringle Modified t-PA with kringle-/replaced by another kringle

1991-08-12

1992-09-22

Lacey, David L.

Drug, bio-affecting and body treating compositions

Enzyme or coenzyme containing

Hydrolases

424 9463, 435226, 4352402, 4352523, 4353201, 435217, 435214, 536 27, 530324, A61K 37547, C12N 964, C12N 1558, C07H 2104

Patent

active

051495333

ABSTRACT:
Tissue plasminogen activator analogs exhibiting greater specificity for fibrin than native t-PA are disclosed. The analogs include the K1 domain of native t-PA replaced with another kringle domain mediating the binding of the analog to fibrin. The kringle contains six cysteine residues. The t-PA analogs may further include a variety of substitutions and modifications. Pharmaceutical compositions containing one or more of the t-PA analogs along with a physiologically acceptable carrier or diluent are also disclosed.

REFERENCES:
patent: 4766075 (1988-08-01), Goeddel et al.
Pennica et al., "Cloning and Expression of Human Tissue-type Plasminogen Activator cDNA in E. coli", Nature 301:214-221, 1983.
Degan et al., "Characterization of the Complementary Deoxyribonucleic Acid and Gene Coding for Human Prothrombin", Biochemistry 22:2087-2097, 1983.
Banyai et al., "Common Evolutionary Origin of the Fibrin-binding Structures of Fibronectin and Tissue-type Plasminogen Activator", FEBS Lett. 163:37-41, 1983.
Vali and Patthy, "The Fibrin-binding Site of Human Plasminogen", J. Biol. Chem. 259:13690-13694, 1984.
Wang et al., "Site-Specific Mutagenesis of Human Interleukin-2 Gene: Structure-Function Analysis of the Cysteine Residues", Science 224:1431-1433, 1984.
van Zonneveld et al., "On the Relation Between Structure and Function of Human Tissue-type Plasminogen Activator", Throm. Haemostas. 54:4,1985.
Kagitani et al., "Expression in E. coli of Finger-domain Lacking Tissue-type Plasminogen Activator with High Fibrin Affinity", FEBS Lett. 189:145-149, 1985.
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Collen, "On the Regulation and Control of Fibrinolysis", Throm. Haemostas. 43:77-89, 1980.
Hoylaerts et al., "Kinetics of the Activation of Plasminogen by Human Tissue Plasminogen Activator", J. Biol. Chem. 257:2912-2919, 1982.
Edlund et al., "Isolation of cDNA Sequences Coding for a Part of Human Tissue Plasminogen Activator", Proc. Natl. Acad. Sci. USA 80:349-352, 1983.

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